The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 to 6

Day 1 to 4

Dexamethasone

40 mg (PO)

ONCE a day on days 1 to 4. Take in the morning with food.

Melphalan

10 mg/m2 (PO)

ONCE a day on days 1 to 4. Take on an empty stomach at least one hour before, or two hours after food.*

* Consider starting melphalan at a 50% dose reduction for patients older than 75 years.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 to 6

Day 1 to 4

Dexamethasone

40 mg (PO)

ONCE a day on days 1 to 4. Take in the morning with food.

Melphalan

10 mg/m2 (PO)

ONCE a day on days 1 to 4. Take on an empty stomach at least one hour before, or two hours after food.*

* Consider starting melphalan at a 50% dose reduction for patients older than 75 years.

No antiemetics should be routinely administered before treatment in patients without a history of nausea and vomiting. If patients experience nausea and/or vomiting, consider using the low antiemetic prophylaxis regimen.

Diabetic patients should monitor their blood glucose levels closely. To minimise gastric irritation, advise patient to take immediately after food. Consider the use of a H2 antagonist or proton pump inhibitor if appropriate.

Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the antineoplastic regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient​ preferences. Suggested dose modifications are based on clinical trial findings, product information and reference committee consensus. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Note: All dose reductions are calculated as a percentage of the starting dose

Haematological toxicity

ANC x 109/L, Platelets x 109/L (pre-treatment blood test)

Myelosuppression from melphalan is cumulative from which recovery can be prolonged or incomplete.

Neutrophils less than 1.0 and/or platelets less than 75

Delay melphalan until recovery unless due to marrow infiltration and consider dose reduction on subsequent cycles

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.

Digoxin

Antineoplastic agents can damage the lining of the intestine; affecting the absorption of digoxin

Monitor digoxin serum levels; adjust digoxin dosage as appropriate

Antiepileptics

Both altered antiepileptic and antineoplastic levels may occur, possibly leading to loss of efficacy or toxicity

Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the antineoplastic therapy

Diminished response to vaccines and increased risk of infection with live vaccines

Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

Prophylaxis medications

Patient information

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

The evidence supporting this protocol is provided by two key studies.The first study was a phase III single centre randomised trial involving 100 patients comparing melphalan plus dexamethasone (Mel-Dex) with HDM/ASCT in patients with AL amyloidosis. Between 2000 and 2005, 50 patients were randomised to receive Mel-Dex (melphalan 10mg/m2 PO D1 to 4, dexamethasone 40mg PO D1 to 4 every 28 days for up to 12 cycles), and 50 patients were randomised to receive HDM/ASCT (IV melphalan 200mg/m2, or 140mg/m2 if age >65 or significant cardiac, renal or hepatic dysfunction). The primary end point was overall survival. Only 37/50 patients in the HDM/ASCT arm received the assigned treatment, mostly due to early deaths, and the treatment-related mortality rate was 24%. There were no treatment-related deaths in the Mel-Dex arm. On intention-to-treat analysis, Mel-Dex produced superior overall survival with comparable haematologic and organ response rates to HDM/ASCT.r

The second study was a phase II Italian study of 46 patients considered ineligible for high-dose melphalan/autologous haematopoietic stem cell transplantation (HDM/ASCT). Patients were treated with melphalan 0.22mg/kg PO D1 to 4 and dexamethasone 40mg PO D1 to 4 every 28 days. Treatment was continued for up to 9 cycles in responding patients, or until achievement of complete haematologic response, biochemical progression, or significant toxicity. The study concluded that Mel-Dex was feasible and well-tolerated in AL patients ineligible for HDM/ASCT.rr

Efficacy

In the phase III RCT by Jaccard et al, after a median follow up of 24 months, the median OS by intention-to-treat analysis was 56.9 months in the Mel-Dex group and 22.2 months in the HDM/ASCT group (HR=0.57; CI 95% 0.32 to 0.99 ; p=0.05; see graph). A landmark analysis of surviving patients at 6 months post-randomisation who received their assigned treatment showed no difference in overall survival between the two treatment arms. Haematologic and organ responses were also not significantly different between armsr (see table below).

In the phase II study by Palladini et al patients were followed for a median of 5 years. The median progression-free survival and overall survival were 3.8 years and 5.1 years, respectively. Four patients developed biochemical relapse from CR at a median of 2.0 years, but all were successfully treated back to CR with further Mel-Dex.r

Toxicity

Toxicities reported in the Mel-Dex arm of the Jaccard study included sepsis (23%), cytopenias (42%) and steroid-induced diabetes mellitus (2%).r The phase II study by Palladini et al reported grade 3/4 toxicity in 11% of patients, including respiratory infection, cytopenias and one case of myelodysplastic syndrome. Disease-related causes accounted for the majority of deaths, in both responding and non-responding patients.r

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Protocol reviewed using the stratified review process at the Haematology Reference Committee meeting.
No changes, review again in 2 years.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au